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https://www.readbyqxmd.com/read/29165315/an-expression-screen-for-aged-dependent-micrornas-identifies-mir-30a-as-a-key-regulator-of-aging-features-in-human-epidermis
#1
Charlotte Muther, Lara Jobeili, Maëlle Garion, Sandrine Heraud, Amélie Thepot, Odile Damour, Jérôme Lamartine
The mechanisms affecting epidermal homeostasis during aging remain poorly understood. To identify age-related microRNAs, a class of non-coding RNAs known to play a key role in the regulation of epidermal homeostasis, an exhaustive miRNA expression screen was performed in human keratinocytes from young or elderly subjects. Many microRNAs modulated by aging were identified, including miR-30a, in which both strands were overexpressed in aged cells and epidermal tissue. Stable MiR-30a over-expression strongly impaired epidermal differentiation, inducing severe barrier function defects in an organotypic culture model...
November 19, 2017: Aging
https://www.readbyqxmd.com/read/29163763/pd-l1-expression-and-cd8-tumor-infiltrating-lymphocytes-are-associated-with-alk-rearrangement-and-clinicopathological-features-in-inflammatory-myofibroblastic-tumors
#2
Yoon Jin Cha, Hyo Sup Shim
Background: Inflammatory myofibroblastic tumors (IMTs) are rare mesenchymal neoplasms that are composed of myofibroblastic cells accompanied by inflammatory infiltrate. We investigated the immune profiles of IMTs, including PD-L1 expression and proportion of CD8+ tumor-infiltrating lymphocytes (TILs), as well as its clinicopathological characteristics according to ALK gene rearrangementstatus. Methods: Twenty-eight IMTs from 25 patients were retrieved from our pathology files (2005-2015), and their clinicopathological parameters and outcomes were analyzed...
October 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/29163706/igfbp-4-expression-is-adversely-associated-with-lung-cancer-prognosis
#3
Yang Xiao, Shan Zhu, Wen Yin, Xiaofan Liu, Yi Hu
Insulin-like growth factor binding protein-4 (IGFBP-4) was reported to be associated with prognosis in several types of cancer; however, to the best of our knowledge, whether it is correlated with lung cancer has yet to be reported. In the present study, 102 pairs of lung cancer tissues and surrounding non-cancerous tissues (SNCTs) were collected. The IGFBP-4 levels in tissues were detected with immunohistochemistry. The relevance of IGFBP-4 to the survival of patients was assessed. The IGFBP-4 gene was knocked down, and its function in the proliferation of lung cancer cells was measured...
December 2017: Oncology Letters
https://www.readbyqxmd.com/read/29162237/inter-individual-gene-variants-associated-with-trabecular-bone-plasticity-a-step-forward-in-the-personal-genomics-of-degenerative-bone-disease
#4
Enrique Caso, Cristina C Sabiers, Daniel López-Guillén, Jaime Caso, Manuel Toledano, Raquel Osorio, Estrella Osorio, Carmen Lozano, Enrique Guerado
Continuing tissue destruction in osteoarthrosis is maintained by molecular pathways related to an unbalanced chondrocyte metabolism, the loss of reactive oxygen species (ROS) homeostasis, increase catabolism in a degraded matrix and the limited response to growth factors due to cell aging. Rare deleterious gene variants driving relevant molecular pathways may play a key role in the pathogenesis and genetic control of common diseases and may also influence the common gene variants observed in GWAS. We use molecular profiling technologies based on massive sequencing of genes to interrogate clinical samples for a variety of molecules involved in the pathogenesis pathways of OA and also to derive new insights for drug targeting discovery at an early stage of the disease...
November 2017: Injury
https://www.readbyqxmd.com/read/29160127/the-fetal-programming-effect-of-prenatal-smoking-on-igf1r-and-igf1-methylation-is-organ-and-sex-specific
#5
Karolin F Meyer, Rikst Nynke Verkaik-Schakel, Wim Timens, Lester Kobzik, Torsten Plösch, Machteld N Hylkema
The impact of prenatal smoke exposure (PSE) on DNA methylation has been demonstrated in blood samples from children of smoking mothers, but evidence for sex-dependent smoke-induced effects is limited. As the identified differentially methylated genes can be associated with developmental processes, and insulin-like growth factors (IGFs) play a critical role in prenatal tissue growth, we hypothesized that PSE induces fetal programming of Igf1r and Igf1. Using a mouse model of smoking during pregnancy, we show that PSE alters promoter methylation of Igf1r and Igf1 and deregulates their gene expression in lung and liver of fetal (E17...
November 21, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/29157899/epidemiology-of-diabetic-foot-infections-in-a-reference-tertiary-hospital-in-india
#6
Sanjith Saseedharan, Manisa Sahu, Roonam Chaddha, Edwin Pathrose, Arun Bal, Pallavi Bhalekar, Priyadharshini Sekar, Padma Krishnan
INTRODUCTION: The present study attempts to examine the microbial profile and antibiotic susceptibility of diabetic foot infections in the intensive care unit of a tertiary referral centre for diabetic foot. As part of the study, we also attempted to find the prevalence of blaNDM-like gene among carbapenem-resistant gram negative infections. METHODOLOGY: A prospective study of 261 patients with diabetic foot infections was performed during the period between January 2014 and June 2014...
November 1, 2017: Brazilian Journal of Microbiology: [publication of the Brazilian Society for Microbiology]
https://www.readbyqxmd.com/read/29156695/mir-2964a-5p-binding-site-snp-regulates-atm-expression-contributing-to-age-related-cataract-risk
#7
Han Rong, Shanshan Gu, Guowei Zhang, Lihua Kang, Mei Yang, Junfang Zhang, Xinyue Shen, Huaijin Guan
This study was to explore the involvement of DNA repair genes in the pathogenesis of age-related cataract (ARC). We genotyped nine single nucleotide polymorphisms (SNPs) of genes responsible to DNA double strand breaks (DSBs) in 804 ARC cases and 804 controls in a cohort of eye diseases in Chinese population and found that the ataxia telangiectasia mutated (ATM) gene-rs4585:G>T was significantly associated with ARC risk. An in vitro functional test found that miR-2964a-5p specifically down-regulated luciferase reporter expression and ATM expression in the cell lines transfected with rs4585 T allele compared to rs4585 G allele...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156006/diana-tarbase-v8-a-decade-long-collection-of-experimentally-supported-mirna-gene-interactions
#8
Dimitra Karagkouni, Maria D Paraskevopoulou, Serafeim Chatzopoulos, Ioannis S Vlachos, Spyros Tastsoglou, Ilias Kanellos, Dimitris Papadimitriou, Ioannis Kavakiotis, Sofia Maniou, Giorgos Skoufos, Thanasis Vergoulis, Theodore Dalamagas, Artemis G Hatzigeorgiou
DIANA-TarBase v8 (http://www.microrna.gr/tarbase) is a reference database devoted to the indexing of experimentally supported microRNA (miRNA) targets. Its eighth version is the first database indexing >1 million entries, corresponding to ∼670 000 unique miRNA-target pairs. The interactions are supported by >33 experimental methodologies, applied to ∼600 cell types/tissues under ∼451 experimental conditions. It integrates information on cell-type specific miRNA-gene regulation, while hundreds of thousands of miRNA-binding locations are reported...
November 16, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29155983/meox1-accelerates-myocardial-hypertrophic-decompensation-through-gata4
#9
Dan Lu, Jizheng Wang, Jing Li, Feifei Guan, Xu Zhang, Wei Dong, Ning Liu, Shan Gao, Lianfeng Zhang
Aims: Pathological hypertrophy is the result of gene network regulation, which ultimately leads to adverse cardiac remodelling and heart failure (HF), and is accompanied by the reactivation of a 'foetal gene programme'. The Mesenchyme homeobox 1 (Meox1) gene is one of the foetal programme genes. Meox1 may play a role in embryonic development, but its regulation of pathological hypertrophy is not known. Therefore, this study investigated the effect of Meox1 on pathological hypertrophy, including familial and pressure overload-induced hypertrophy, and its potential mechanism of action...
November 16, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/29155979/epigenetic-editing-of-the-dlg4-psd95-gene-improves-cognition-in-aged-and-alzheimer-s-disease-mice
#10
Fernando J Bustos, Estibaliz Ampuero, Nur Jury, Rodrigo Aguilar, Fahimeh Falahi, Jorge Toledo, Juan Ahumada, Jaclyn Lata, Paula Cubillos, Berta Henríquez, Miguel V Guerra, Jimmy Stehberg, Rachael L Neve, Nibaldo C Inestrosa, Ursula Wyneken, Marco Fuenzalida, Steffen Härtel, Miguel Sena-Esteves, Lorena Varela-Nallar, Marianne G Rots, Martin Montecino, Brigitte van Zundert
The Dlg4 gene encodes for post-synaptic density protein 95 (PSD95), a major synaptic protein that clusters glutamate receptors and is critical for plasticity. PSD95 levels are diminished in ageing and neurodegenerative disorders, including Alzheimer's disease and Huntington's disease. The epigenetic mechanisms that (dys)regulate transcription of Dlg4/PSD95, or other plasticity genes, are largely unknown, limiting the development of targeted epigenome therapy. We analysed the Dlg4/PSD95 epigenetic landscape in hippocampal tissue and designed a Dlg4/PSD95 gene-targeting strategy: a Dlg4/PSD95 zinc finger DNA-binding domain was engineered and fused to effector domains to either repress (G9a, Suvdel76, SKD) or activate (VP64) transcription, generating artificial transcription factors or epigenetic editors (methylating H3K9)...
November 16, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/29155255/the-role-of-epigenetics-in-cardiovascular-health-and-aging-a-focus-on-physical-activity-and-nutrition
#11
REVIEW
Robert G Wallace, Laura C Twomey, Marc-Antoine Custaud, Jonathan Turner, Niall Moyna, Philip M Cummins, Ronan P Murphy
The cardiovascular system is responsible for transport of blood and nutrients to tissues, and is pivotal to the physiological health and longevity. Epigenetic modification is a natural, age-associated process resulting in highly contextualised gene expression with clear implications for cell differentiation and disease onset. Biological/epigenetic age is independent of chronological age, constituting a highly reflective snapshot of an individual's overall health. Accelerated vascular aging is of major concern, effectively lowering disease threshold...
November 16, 2017: Mechanisms of Ageing and Development
https://www.readbyqxmd.com/read/29155150/enhancement-of-cutaneous-immunity-during-ageing-by-blocking-p38-mapkinase-induced-inflammation
#12
Milica Vukmanovic-Stejic, Emma S Chambers, Mayte Suarez- Farinas, Daisy Sandhu, Judilyn Fuentes-Duculan, Neil Patel, Elaine Agius, Katie E Lacy, Carolin T Turner, Anis Larbi, Veronique Birault, Mahdad Noursadeghi, Neil A Mabbott, Malcolm H A Rustin, James Krueger, Arne N Akbar
BACKGROUND: Immunity declines with age that leads to re-activation of varicella zoster virus (VZV). In humans, age associated immune changes are usually measured in blood leukocytes however this may not reflect alterations in tissue-specific immunity. OBJECTIVES: We used a VZV antigen challenge system in the skin to investigate changes in tissue specific mechanisms involved in the decreased response to this virus during ageing. METHODS: We assessed cutaneous immunity by the extent of erythema and induration after intradermal VZV antigen injection...
November 16, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29154276/sparcl1-accelerates-symptom-onset-in-alzheimer-s-disease-and-influences-brain-structure-and-function-during-aging
#13
Sahba Seddighi, Vijay R Varma, Yang An, Sudhir Varma, Lori L Beason-Held, Toshiko Tanaka, Melissa H Kitner-Triolo, Michael A Kraut, Christos Davatzikos, Madhav Thambisetty
We recently reported that alpha-2 macroglobulin (A2M) is a biomarker of neuronal injury in Alzheimer's disease (AD) and identified a network of nine genes co-expressed with A2M in the brain. This network includes the gene encoding SPARCL1, a protein implicated in synaptic maintenance. Here, we examine whether SPARCL1 is associated with longitudinal changes in brain structure and function in older individuals at risk for AD in the Baltimore Longitudinal Study of Aging. Using data from the Gene-Tissue Expression Project, we first identified two single nucleotide polymorphisms (SNPs), rs9998212 and rs7695558, associated with lower brain SPARCL1 gene expression...
November 16, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29154238/ctrc-gene-polymorphism-may-increase-pancreatic-cancer-risk-preliminary-study
#14
Stanisław Głuszek, Artur Kowalik, Dorota Kozieł, Iwona Wawrzycka, Martyna Głuszek-Osuch, Jarosław Matykiewicz
Pancreatic cancer is often fatal due to delayed diagnosis and treatment difficulties. OBJECTIVE: To analyze selected SPINK1, CTRC, CFTR, and PRSS1 gene mutations in cancer tissue and blood samples of patients with pancreatic tumors. MATERIALS AND METHOD: We enrolled 16 consecutive patients diagnosed with pancreatic tumors. We collected cancer tissue, normal pancreatic tissue, and blood samples for genetic tests. The control group consisted of 419 healthy individuals...
October 31, 2017: Polski Przeglad Chirurgiczny
https://www.readbyqxmd.com/read/29150696/impact-of-prolonged-overfeeding-on-skeletal-muscle-mitochondria-in-healthy-individuals
#15
Frederico G S Toledo, Darcy L Johannsen, Jeffrey D Covington, Sudip Bajpeyi, Bret Goodpaster, Kevin E Conley, Eric Ravussin
AIMS/HYPOTHESES: Reduced mitochondrial capacity in skeletal muscle has been observed in obesity and type 2 diabetes. In humans, the aetiology of this abnormality is not well understood but the possibility that it is secondary to the stress of nutrient overload has been suggested. To test this hypothesis, we examined whether sustained overfeeding decreases skeletal muscle mitochondrial content or impairs function. METHODS: Twenty-six healthy volunteers (21 men, 5 women, age 25...
November 17, 2017: Diabetologia
https://www.readbyqxmd.com/read/29149836/are-there-different-kinds-of-aging
#16
Amalia Gabriela Diaconeasa
A critical analysis of the accelerated aging syndromes may explain what aging is, but also why some tissues and organs age at accelerated rates in comparison with aging rates of other tissues. Syndromes of accelerated aging are caused by mutations affecting the integrity of the genetic material. Among them, the most studied is Werner's syndrome, "adult progeria", caused by a recessive autosomal mutation with a frequency of 1 in 10 millions, which affects a helicase involved in DNA repair. In Werner syndrome, there is a loss of heterochromatin, though the stability of heterochromatin is also affected in "normal" aging...
November 16, 2017: Current Aging Science
https://www.readbyqxmd.com/read/29149261/glut10-maintains-the-integrity-of-major-arteries-through-regulation-of-redox-homeostasis-and-mitochondrial-function
#17
Yu-Wei Syu, Hao-Wen Lai, Chung-Lin Jiang, Hong-Yuan Tsai, Chung-Chih Lin, Yi-Ching Lee
Glucose transporter 10 (GLUT10) is a member of the GLUT family of membrane transporters, and mutations in this gene cause arterial tortuosity syndrome (ATS). However, the physiological role and regulation of GLUT10 in arteries remains unclear. To further understand its physiological roles in major arteries, we examined the regulatory mechanisms of GLUT10 in ASMCs and aortic tissues. Interestingly, we find that targeting of GLUT10 to mitochondria is increased in ASMCs under both stress and aging conditions, which enhances dehydroascorbic acid (DHA) uptake and maintains intracellular ascorbic acid (AA) levels...
November 15, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/29149221/dietary-protein-sources-differentially-affect-microbiota-mtor-activity-and-transcription-of-mtor-signaling-pathways-in-the-small-intestine
#18
Soumya K Kar, Alfons J M Jansman, Nirupama Benis, Javier Ramiro-Garcia, Dirkjan Schokker, Leo Kruijt, Ellen H Stolte, Johanna J Taverne-Thiele, Mari A Smits, Jerry M Wells
Dietary protein sources can have profound effects on host-microbe interactions in the gut that are critically important for immune resilience. However more knowledge is needed to assess the impact of different protein sources on gut and animal health. Thirty-six wildtype male C57BL/6J mice of 35 d age (n = 6/group; mean ± SEM body weight 21.9 ± 0.25 g) were randomly assigned to groups fed for four weeks with semi synthetic diets prepared with one of the following protein sources containing (300 g/kg as fed basis): soybean meal (SBM), casein, partially delactosed whey powder, spray dried plasma protein, wheat gluten meal and yellow meal worm...
2017: PloS One
https://www.readbyqxmd.com/read/29148577/mouse-models-to-evaluate-the-role-of-estrogen-receptor-%C3%AE-in-skeletal-maintenance-and-adaptation
#19
REVIEW
Amanda M Rooney, Marjolein C H van der Meulen
Estrogen signaling and mechanical loading have individual and combined effects on skeletal maintenance and adaptation. Previous work investigating estrogen signaling both in vitro and in vivo using global estrogen receptor α (ERα) gene knockout mouse models has provided information regarding the role of ERα in regulating bone mass and adaptation to mechanical stimulation. However, these models have inherent limitations that confound interpretation of the data. Therefore, recent studies have focused on mice with targeted deletion of ERα from specific bone cells and their precursors...
November 17, 2017: Annals of the New York Academy of Sciences
https://www.readbyqxmd.com/read/29147603/age-estrogen-and-immune-response-in-breast-adenocarcinoma-and-adjacent-normal-tissue
#20
David A Quigley, Andliena Tahiri, Torben Lüders, Margit H Riis, Allan Balmain, Anne-Lise Børresen-Dale, Ida Bukholm, Vessela Kristensen
Chronic inflammation promotes breast tumor growth and invasion by accelerating angiogenesis and tissue remodeling in the tumor microenvironment. There is a complex relationship between inflammation and estrogen, which drives the growth of 70 percent of breast tumors. While low levels of estrogen exposure stimulate macrophages and other inflammatory cell populations, very high levels are immune suppressive. Breast tumor incidence is increased by obesity and age, which interact to influence inflammatory cell populations in normal breast tissue...
2017: Oncoimmunology
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